AB0530 DESIGN OF 2 PHASE 3, DOUBLE-BLIND, PLACEBO-CONTROLLED, GLOBAL TRIALS OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYROSINE KINASE 2 (TYK2) INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: C. Arriens, A. Askanase, R. Furie, E. F. Morand, R. Van Vollenhoven, K. Connors, M. Davey, N. Delev, V. Shah, A. Stevens, T. Wegman, C. Hobar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis <sup>[1,2]</sup>. Deucravacitinib demonstrated efficacy across the primary endpoint and all key secondary endpoints in a phase 2 trial in patients with systemic lupus erythematosus (SLE) <sup>[3]</sup>. <h3>Objectives</h3> Here, we describe 2 phase 3 trials currently underway to assess the efficacy and safety of deucravacitinib in patients with active SLE. These phase 3 trials have been designed to replicate the successful elements of the phase 2 trial, including its glucocorticoid-tapering strategy and rigorous management structure <sup>[3]</sup>. <h3>Methods</h3> <b>I</b>n these phase 3, randomized, double-blind, placebo-controlled, global trials (POETYK SLE-1 [NCT05617677], POETYK SLE-2 [NCT05620407]), adults (aged 18-75) with active SLE on background standard-of-care treatment will be randomized (1:1) to placebo or deucravacitinib for 52 weeks of double-blind treatment (<b>Figure 1</b>). Patients on glucocorticoids will be instructed to taper, unless significant disease activity is present, to a threshold dose level during the double-blind treatment period. At week 52, patients may choose to continue in a 104-week open-label extension phase, in which all patients receive deucravacitinib. Key eligibility criteria and study design are depicted below (<b>Figure 1</b>). The primary endpoint of SLE Responder Index (SRI[4]) and all secondary endpoints will be assessed at week 52 (<b>Table 1</b>). Safety and tolerability will be assessed throughout the trial. <h3>Results</h3> Planned randomization in each trial includes 490 patients (245 per treatment group) in 27 countries across North and South America, Europe, and Asia-Pacific. <h3>Conclusion</h3> The phase 3 POETYK SLE trials will further evaluate the efficacy and safety of deucravacitinib, an oral, selective, TYK2 inhibitor, in patients with active SLE. <h3>References</h3> [1]Armstrong A, et al. <i>J Am Acad Dermatol.</i> 2022;S0190-9622(22)02256-3. [2]Strober B, et al. <i>J Am Acad Dermatol.</i> 2022;S0190-9622(22)02643-3. [3]Morand E, et al. <i>Arthritis Rheumatol.</i> 2022; Nov 11 (Epub ahead of print). doi: 10.1002/art.42391. <h3>Acknowledgements</h3> This study was sponsored by Bristol Myers Squibb. <h3>Disclosure of Interests</h3> Cristina Arriens Speakers bureau: AstraZeneca, Aurinia, Bristol Myers Squibb, GlaxoSmithKline, Kezar, AstraZeneca and Aurinia, Grant/research support from: AstraZeneca and Bristol Myers Squibb, Anca Askanase Consultant of: Abbvie, Amgen, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, GlaxoSmithKline, Idorsia, Janssen, Pfizer, and UCB, Richard Furie Consultant of: Bristol Myers Squibb, Grant/research support from: Bristol Myers Squibb, Eric F. Morand Consultant of: AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, Gilead, Novartis, and Servier, Grant/research support from: AbbVie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, and UCB, Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, Janssen, Pfizer, UCB, Consultant of: UCB, Pfizer, AstraZeneca, Biogen, Biotest, Celgene, Gilead, Servier, AbbVie, Galapagos, and Janssen, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Pfizer, UCB, Roche, and GlaxoSmithKline, Kevin Connors Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Monica Davey Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Nikolay Delev Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Vaishali Shah Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Anna Stevens Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Wegman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Coburn Hobar Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb.